tbuckley/cabot-search huggingface dataset:
Immunologic constant of rejection as a predictive biomarker of immune checkpoint inhibitors efficacy in non-small cell lung cancer.
Authors: Alice Mogenet, Laurent Greillier, Emilie Denicolai, Fabrice Barlesi, Francois Bertucci, Pascal Finetti, Pascale Tomasini
Journal: Journal of Clinical Oncology (2023)

e21162 Background: Immune checkpoint inhibitors (ICI) transformed non-small cell lung cancer (NSCLC) prognosis but response rate remains disappointing. Besides PDL1 expression, tumor mutational burden, quantification of tumor infiltrating lymphocytes or methylation profile failed to confirm their predictive role. The ICR (Immunologic Constant of Rejection) signature is defined as an immune phenotype quantifying the expression of 20 genes all involved in cancer immunity. Our first objective was the assessment of ICR signature predictive value and our secondary objectives were to compare ICR signature with other published immune signatures and to assess the prognostic value of ICR signature. Methods: Our series included 77 paraffin-embedded (FFPE) tumors derived from NSCLC patients treated with ICI as a single agent in at least the second line setting. We also collected clinical and biological data from 4 public data sets to expand and confront our local data. Transcriptomic analysis was performed using nCountertechnology Dx analysis by Nanostring based on microscopic imaging counting relative abundance of hundreds of transcripts using the “nCounter PanCancer Immune Profiling Panel” including the 20 ICR genes. Results: We applied the ICR classification to a series of 44 local tumor samples enhanced with 118 samples from public datasets. Hierarchical clustering on both local cohort and public datasets allowed us to distinguish the four ICR classes, from ICR 1 (“cold” tumors) to ICR 4 (“hot” tumors). Among the 5 datasets, we did not observe any significant difference between ICR groups for age, sex and smoking status. We observed a relative homogeneity in Durable Clinical Benefit (DCB) rate among ICR groups 2 to 4 (median DCB above 20%) unlike ICR group 1 (median DCB under 10%) leading us to consider ICR as a binary signature (ICR 1 vs ICR 2-4). ICR signature indeed showed a significant association with DCB among the 5 pooled datasets (OR = 4.40 [95% Confidence Interval 1.44-13.45] p = 0.950) with uniform distribution between them. Then, we conducted a logistic regression univariate analysis of DCB among various previously published immune signatures and ICR signature was the only one to show a significant association with DCB in this analysis ( p = 0.007). Conclusions: We identified a feasible transcriptomic signature with a promising signal of ICI efficacy prediction in the so far disappointing immune biomarkers field. In a near future, predict ICI efficacy will be a major challenge with three pivotal questions. When, balanced with the new data on ICI use in early-stage lung cancer or widely pretreated patients. How, assessing various techniques to develop composite signatures to better consider every driver of immune response. What, considering the amount of potential new therapeutic targets, starting by the 20 genes of ICR signature.
Efficacy of BNT162b2 vaccine and its correlation with serum vitamin D in staff at the national comprehensive cancer center in slovakia.
Authors: Jan Slopovsky, Silvia Cingelova, Alena Svobodova, Lucia Skokanova-Krempaska, Katarina Rejlekova, Robert Babela, Lubos Drgona, Michal Mego, Martina Vulganova, Juraj Pechan, Patrik Palacka
Journal: Journal of Clinical Oncology (2023)

e24037 Background: With established efficacy and safety, BNT162b2 was one of the first licensed mRNA vaccines against SARS-CoV-2. However, it is unclear whether vitamin D serum concentrations affect vaccine efficacy after three doses. Methods: This prospective, single-center study included 273 staff members (85.4% females) of the National Cancer Comprehensive Center in Slovakia. Median age of participants was 47 years (range: 22–80) and median body mass index (BMI) was 24.8 (16.3–44.6) kg/m 2 . The primary objective was to determine the efficacy of BNT162b2 defined as no Covid-19 disease ≥7 days after its administration. The secondary objective was to monitor IgG neutralizing antibodies and total vitamin D in serum after vaccination and test the hypothesis on correlation of total vitamin D concentrations with the vaccine efficacy. If appropriate, results were stratified by gender (males vs females) and BMI ( &lt; 30 vs ≥30 kg/m 2 ). Results: At median follow-up of 4.7 (2.9–5.0) months, vaccine efficacy was 86.1%. The most common adverse events (AEs) were injection site pain (73.3%), fatigue (44.0%), and limb pain (33.0%). No grade 3/4 AEs were observed. Median time from vaccine administration to measurement of IgG and vitamin D concentrations was 3.4 (2.1-4.8) months. IgG concentrations were significantly higher in males compared to females, as well as in subjects with high vs low BMI ( p&lt; 0.0004 and p&lt; 0.0001, respectively). Total vitamin D concentrations were significantly lower in individuals with high vs low BMI ( p&lt; 0.0144). No differences in the rate of Covid-19 positivity were identified based on gender, BMI, and total vitamin D concentrations. Conclusions: This study confirmed high efficacy of third dose of the BNT162b2 vaccine with an acceptable safety profile. The vaccine efficacy was not affected by gender, BMI, and total vitamin D concentrations. These results suggest that serum vitamin D monitoring after third BNT162b2 dose is not beneficial for an estimation of its efficacy. This study was supported by the National Cancer Institute, Bratislava, Slovakia &amp; OncoReSearch, Rovinka, Slovakia. Keywords: BNT162b2; total vitamin D; efficacy; safety profile; IgG.
Risk of severe toxicity from topical fluoropyrimidine treatment in patients carrying <i>DPYD</i> variant alleles.
Authors: Javier Granados, Amy Pasternak, Norah Lynn Henry, Vaibhav Sahai, Daniel Louis Hertz
Journal: Journal of Clinical Oncology (2023)

12123 Background: Patients carrying variant alleles of DPYD that reduce activity of dihydropyrimidine dehydrogenase have unacceptably high risk of severe toxicity from systemic fluoropyrimidine chemotherapy. DPYD testing prior to systemic fluoropyrimidine treatment is standard of care across Europe and is increasingly used in USA. There is a published case report of fatal toxicity from topical fluoropyridine chemotherapy in a DPYD variant carrier, but the risk of severe toxicity in these patients is unknown. This information is critical to determine whether patients receiving topical fluoropyrimidine treatment should also undergo DPYD genetic testing. The objective of this retrospective cohort study was to determine whether patients carrying DPYD variant alleles have increased risk of severe toxicity from topical fluoropyrimidine treatment. Methods: Individuals who received topical fluoropyrimidine treatment at Michigan Medicine and had available DPYD genotype data, due to participation in the Michigan Genomics Initiative institutional genetic data repository, were eligible for this analysis. Clinical data for the first cycle of topical fluoropyrimidine treatment was abstracted from the electronic medical record by an investigator blinded to genetic data. Toxicities were graded based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The primary endpoint was grade 3+ toxicity. The secondary endpoint was grade 1+ toxicity. Genotypes for five validated decreased- or null-activity DPYD variant alleles were included: DPYD*2A (rs3918290), DPYD*13 (rs55886062), DPYD p.D949V (rs67376798) DPYD HapB3 (rs56038477) and DPYD p.Y186C (rs115232898). Toxicity rates in DPYD variant carriers vs. wild-type were compared using Fisher’s Exact tests. Results: 201 patients receiving topical fluoropyrimidine therapy who had available DPYD genotype data were included in the analysis. Most patients were self-reported white (97%), male (71%), and received topical fluoropyrimidine for a diagnosis of actinic keratosis (79%). As expected in a US patient cohort, 7.0% (14/201) of patients carried a DPYD variant. No patients experienced grade 3+ toxicity. Patients carrying a DPYD variant allele had nominally higher risk of grade 1+ toxicity (21.4% vs. 10.2%, odds ratio = 2.40 (95% Confidence Interval: 0.10-2.53), p = 0.19). Conclusions: Patients carrying DPYD variant alleles may have increased risk of non-severe toxicity from topical fluoropyrimidines, but the risk of severe toxicity is minimal regardless of genotype. DPYD genetic testing to prevent severe and fatal fluoropyrimidine toxicity should be reserved for patients receiving systemic treatment and need not include patients receiving topical treatment, in whom risk of severe toxicity is minimal.
Sex differences in prognostic utility of peripheral eosinophil count in first-line immune checkpoint therapy against metastatic NSCLC.
Authors: Hyunwoo Kwon, Mingjia Li, Kenneth Chian, Timothy Gauntner, Nicholas Jones, Adam Khorasanchi, Daniel Spakowicz, Gabrielle Lopez, Evelyn Goodyear, Austin Secor, Kai He, Asrar Alahmadi, Regan Michelle Memmott, Jacob Kaufman, Peter G. Shields, David Paul Carbone, Gregory Alan Otterson, Carolyn J Presley, Zihai Li, Dwight Hall Owen
Journal: Journal of Clinical Oncology (2023)

9067 Background: To date, few studies have associated elevated Absolute Eosinophil Count (AEC) with improved outcome to a single agent immune checkpoint inhibitor (ICI) as first or subsequent line of therapy in patients with NSCLC. Here, we investigated prognostic utility of AEC and the sex difference in patients undergoing standard-of-care first-line ICI with or without chemotherapy for metastatic NSCLC. Methods: This was a retrospective cohort study of 310 patients with Stage IV NSCLC treated with first-line ICI-based therapies (alone or in combination with chemotherapy) under IRB approved protocol 2021C0069. Demographic data are summarized in the table. Peripheral AEC measured by cells/microL was collected within 1 week before the start of therapy. Eosinophil count was evaluated in males and females by both descriptive statistics and Chi-squared test as a continuous and categorical variable, respectively. High level of baseline AEC was defined as 75th percentile (270 cells/microL). Overall Survival (OS) was plotted using the Kaplan-Meier method and p-values from log-rank test were reported. PD‐L1 was assessed by tumor proportion score (TPS) and classified into &lt; 1%, 1 to 49% and ≥ 50%. Results: 14% male vs 6% female patients were found to have peripheral eosinophilia (AEC ≥ 500) at the start of immunotherapy, p = 0.02. Patients with lower AEC had a median OS of 18.6 months vs 29.3 months in those with higher AEC ( p = 0.02, HR: 1.465, 95% Cl: 1.073-2.001). Patients with higher baseline AEC showed a sex difference, with median OS of 23.9 months in males vs NR median OS in females with over 60% survival at the time of last follow up ( p = 0.04, HR: 1.934, 95% Cl: 1.040-3.597). This difference was seen with ICI monotherapy ( p = 0.02, HR: 2.630, 95% Cl: 1.192-5.805), but not ICI with chemotherapy ( p = 0.83, HR: 1.116, 95% Cl: 0.4054-3.070). Higher AEC was associated with TPS ≥ 50% in both males and females ( p = 0.004 and 0.001, respectively), though no significant sex difference was observed. Conclusions: Our data highlight critical sex differences in interpretation of baseline AEC in patients on ICI therapy for metastatic NSCLC. While males have a higher frequency of peripheral eosinophilia, higher AEC correlates to improved OS predominantly in females. Further, this female-biased outcome is seen only with ICI monotherapy, even though higher AEC is associated with high PD-L1 expression in both sexes. Future studies are indicated to assess the longitudinal trend in eosinophil count as well as their active versus passive role in anti-tumor immunity and toxicity in the presence or absence of chemotherapy. [Table: see text]
Trends in application and match outcomes for hematology and oncology fellowship: An analysis of charting outcomes from 2008 to 2022.
Authors: Ademola Samuel Ojo, Ahmed Ali
Journal: Journal of Clinical Oncology (2023)

e23004 Background: The rapidly evolving advances in the field of oncology make it attractive to many internal medicine residents and graduates who must secure a position through the hematology and oncology fellowship match to get a chance to complete training in oncology. We aim to evaluate the trends in the application, competitiveness, and match rates of the hematology and oncology fellowship match based on the category of applicants. Methods: This is a retrospective cohort study of applicants who applied for the hematology and oncology fellowship from 2008 to 2022 based on the match data released by the National Residency Match Program (NRMP). The number of applicants, type of applicants, number of positions, and match outcomes was evaluated. Applicant types were classified into US-allopathic graduates and non-US-allopathic graduates. Chi-square tests were used to compare the match outcomes and the applicant types. Results: A total of 11,357 applicants participated in the hematology and oncology fellowship match during the study period. The number of applicants increased from 724 in 2008 to 894 in 2022 (a 23% increase), while the number of positions increased from 424 to 663 (a 36% increase). The average match rate was 68.5% during the study period, rising from 57.5% in 2008 to 73.5% in 2022. US allopathic graduates have a higher match rate when compared to non-US allopathic graduates (83.8% vs 56.2%; p &lt; 0.00001). Although this disparity is maintained over time, it progressively narrowed (77.2% vs 42.5% in 2008 compared to 85.4% vs 63.3% in 2022). Fifty-three percent of applicants matched in their top 3 programs (36.5% in 1st, 11.2% in 2nd, and 7.3% in 3rd). The percentage of applicants matched in their top 3 programs increased from 53.4% in 2009 to 57.4% in 2022 (range: 50-62%). Conclusions: The hematology and oncology fellowship match is highly competitive with outcomes more favorable to US-allopathic graduates than non-US allopathic graduates. Most successful applicants matched in one of their top three programs. [Table: see text]
Effects of the coronavirus disease 2019 pandemic on anxiety and spirituality in patients with cancer undergoing chemotherapy: A cross-sectional study.
Authors: Francisca Fernanda Barbosa Oliveira, Rosane Oliveira Sant'Ana, Anna Clara Aragão Matos Carlos, André Alves Crispim, Lívia Moreira Caetano Coelho, Cássia Emanuella Nóbrega Malta, Maria Marcela Fontes Borges, Thuany Pinto Rocha de Souza, Isabelle Joyce de Lima Silva-Fernandes, Clarissa Gondim Picanço-Albuquerque, Lúcio Flávio Gonzaga Silva, Paulo Goberlanio de Barros Silva
Journal: Journal of Clinical Oncology (2023)

e24200 Background: The objective of this study was to evaluate anxiety and spirituality levels in oncology patients during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This short-term cross-sectional study applied a previously validated General Anxiety Disorder-7 (GAD7) scale and spirituality inventory to 230 patients undergoing antineoplastic chemotherapy during the second wave of COVID-19 in Brazil. The means ± SD of the scales were calculated and correlated (Spearman's rho). After categorization, chi-square and multinomial regression models were used to identify risk factors (p &lt; 0.05). Results: The levels of anxiety (6.16±5.11) and spirituality (17.22±2.66) were moderately and inversely correlated (p = 0.001, r = -0.212). Women (p = 0.025), fatigue (p = 0.048), and insomnia (p = 0.001) were associated with an increased incidence of anxiety; however, spirituality was associated with a reduced incidence of fatigue (p = 0.032). Death of family or friends due to COVID-19 increased the risk of high levels of anxiety (p &lt; 0.05), while in multivariate analysis, insomnia (p = 0.030) and sleep difficulty (p = 0.031) were also directly associated with anxiety and spirituality reduced the interruption of chemotherapy during the COVID-19 pandemic (p = 0.036). Conclusions: Fear of the COVID-19 pandemic altered the psychoemotional environment of patients undergoing chemotherapy, resulting in increased levels of anxiety. However, spirituality was an important coping strategy in patients undergoing cancer treatment.
Long-term outcomes of single and five fraction schedules of stereotactic body radiation therapy for early-stage central or peripheral NSCLC: Neither fractionation nor location matter?
Authors: Karen Huang, Sharan Prasad, Sung Jun Ma, Austin Iovoli, Mark Farrugia, Nadia Karen Malik, Anurag K. Singh
Journal: Journal of Clinical Oncology (2023)

8538 Background: Due to concerns with toxicity, treatment of early-stage non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT) often involves different fractionation schemes for peripheral and centrally located tumors. There is a paucity of long-term SBRT survival outcomes comparing peripheral versus central NSCLC. Methods: This is a single-institution observational cohort study of patients diagnosed with early-stage NSCLC (T1-2N0M0) who underwent 27 Gy in 1 fraction or 50 Gy in 5 fractions with heterogeneity correction at Roswell Park Comprehensive Cancer Center between September 2008 to December 2018. All patients treated with single-fraction SBRT had peripheral NSCLC and those treated with five-fraction SBRT had central NSCLC. Clinically relevant variables including age, gender, race, Karnofsky Performance Status (KPS), histology (adenocarcinoma, squamous cell carcinoma, NSCLC not otherwise specified), T stage, smoking status, tumor location, and the year of SBRT delivery were obtained retrospectively. Cox multivariable analysis (MVA), Kaplan-Meier plot, and log-rank test were performed to evaluate progression-free survival (PFS) and overall survival (OS). Fine-Gray competing risk MVA was performed to evaluate local failure (LF), nodal failure (NF), and distant failure (DF) with death as a competing event. To reduce selection bias, propensity score matching was performed between single- versus five-fraction SBRT cohorts. Results: A total of 265 patients (142 female [53.6%]; median age 77 years) met our criteria. There were 74 (27.9%) and 191 (72.1%) patients with central tumors treated with five-fraction SBRT and peripheral tumors treated with single-fraction SBRT, respectively. On Cox MVA, there was no statistically significant difference in OS (peripheral vs central tumors: adjusted hazards ratio [aHR] 1.04, 95% confidence interval [CI] 0.74-1.46, p=0.81) and PFS (peripheral vs central tumors: aHR 1.05, 95% CI 0.76-1.45, p=0.77). On Fine-Gray competing risk MVA comparing peripheral vs. central tumors, there was no statistically significant difference in LF, NF, and DF. After propensity score matching, 68 matched pairs were identified for peripheral vs. central tumors with similar results. Conclusions: Among patients with early-stage NSCLC treated with SBRT central versus peripheral location was associated with similar long-term survival and tumor recurrence outcomes.
Somatic profiling guides germline genetic testing in patients with mutations in cancer predisposition genes.
Authors: Sourat Darabi, Jeanne Homer, Chelsey Weatherill, Carlos E Zuazo, Valentina Dalili-Shoaie, Michael J. Demeure, David R. Braxton
Journal: Journal of Clinical Oncology (2023)

10608 Background: 15% of patients with advanced cancer have an inherited predisposition to cancer. Over a third of patients carrying a pathogenic germline variant would not qualify for genetic testing based on current National Comprehensive Cancer Network genetic testing guidelines. Supplementing the current practice of somatic sequencing with germline testing would improve treatment decisions and be informative of the risk of developing subsequent cancers in the individual. It may also extend the benefits of high-risk screening programs to family members. Offering genetic testing to patients with the highest likelihood of carrying a germline mutation is preferable to unselected sequencing given the current environment. Methods: We developed a list of genes to help identify patients whose somatic mutations were more likely to be found in the germline as well. We classified these genes into 3 tiers based on the likelihood of germline pathogenicity. All somatic sequencing panel results were reviewed based on the IRB-approved protocol for our designated Tier One genes ( ATM, BAP1, BMPR1A, BRCA1, BRCA2, BRIP1, MSH2, MSH6, MUTYH, MYH11, PALB2, RUNX1, SDHAF2, SDHB, SDHC, and known founder mutations in additional genes). Treating physicians for patients whose tumors harbored a mutation in one of these genes were contacted and, if they agreed, patients were offered participation in this ongoing study. Enrolled patients had genetic counseling and testing for a multi-gene panel at no cost to them. Results: We reviewed 3621 somatic test results, and 339 (9.4%) patients were eligible for the study. 34 (10.03%) eligible patients were enrolled, and 33 (9.73%) completed testing. Of these, 16 had positive germline results (48.5%, though they may not all be in the originally identified genes), 8 had a variant of uncertain significance (24.2%), and 9 had negative testing (27.3%). Some patients were not referred by their treating physicians based on their own clinical assessment. Others were hesitant to enroll due to concerns about the privacy of genetic information. Other confounding factors may have affected our accrual, including the pandemic. Conclusions: Implementing a somatic profiling-based screening program to identify inherited cancer predisposition syndromes is feasible in patients who may not meet current germline genetic testing guidelines. Our study showed 9.73% of eligible patients underwent genetic counseling and testing, and an inherited predisposition to cancer was confirmed in almost 50% of these patients. In addition, family members were offered cascade testing. Germline genetic evaluation remains underutilized even when payor constraints are removed as a barrier. To increase the identification of patients with inherited predispositions to cancer other barriers such as a lack of referrals by treating oncologists need to be overcome.